Transforming growth factor beta1 (TGF-beta1) has been identified as a potentially important intraovarian growth factor due to its pronounced effects upon theca and granulosa cell function and the localization of the growth of work regarding TGF-beta1 and folliculogenesis, there remains a notable deficit in our knowledge regarding its regulation at the cellular level and how this relates to ovarian function. Solving the riddle regarding TGF- beta1 function and regulation represents the long term goals of this project. Using both cultured cells and intact hemi-follicles from the porcine ovary, a model for the regulation of TGF-beta1 expression has been formulated. Data suggest that although both cell types express TGF-beta1mRNA, only theca cells express and secrete the growth factor. Neither FSH, LH, nor cAMP stimulates TGF-beta section in either isolated cell type in culture. In small hemi-follicles, however, FSH but not LH stimulates TGF-beta1 secretion as does cAMP. We hypothesize that theca cells express and secrete TGF-beta1 during follicle development but that it is under the direction of FSH acting upon granulosa cells. We further hypothesize that a FSH-stimulated granulosa cell product regulates theca cell TGF-beta expression by activating the PLA/PKC signal transduction system. To further delineate the inter-follicular regulation of TGF-beta1 it will be established whether TGF- beta1 auto expression occurs in granulosa but not theca cells, whether this is mediated by selective expression of TGF-beta type I and II receptors, and whether auto-expression or receptor expression change with follicle development. The extent to which FSH and TGF-beta1 reciprocally regulate the expression of the other receptor in granulosa cells will be determined. The extent to which granulosa cells can directly regulate theca cell TGF- beta1 expression via secretory factors will be tested by co-culture experiments. Whether follicular TGF-beta1 expression switches from FSH to LH governance with follicle development will be determined. Lastly, the selective granulosa cell expression of a cytosolic protein capable of binding to a regulatory stem-loop structure of the TGF-beta1 mRNA 5'-untranslated region which inhibits translation will be investigated. This may be the mechanism by which granulosa cells differentially express TGF-beta1 mRNA but not the growth factor. It is believed that completion of the studies described herein will provide novel and important information regarding inter-follicular, paracrine regulation of TGF-beta1, which will provide insight into its role during follicle development.